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Investigation of Aspects Important in the Structural Assembly of Human Septin Filaments

Grant number: 12/00268-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): July 01, 2012
Effective date (End): August 31, 2015
Field of knowledge:Biological Sciences - Biophysics - Molecular Biophysics
Principal Investigator:Richard Charles Garratt
Grantee:Sabrina Matos de Oliveira da Silva
Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil


Septins comprise a conserved family of filament forming guanine binding proteins. They have been associated with certain diseases in eukaryotes and are involved in a series of important cellular processes. These proteins are so named because of their role in septation during cell division in yeast, where a failure can lead to cell death or irregularities during the cell cycle. However, despite the importance of this class of proteins, little information in available concerning the details of their molecular functions. Particularly the role of GTP binding and hydrolysis as well as the mechanism of polymerization in the form of hetero-oligomers have yet to be completely established. The present proposal is centered on the structural analysis of novel septin complexes. The co-expression and crystallization of four complexes of septins will be attempted. The choice of combinations is based partly on the rules established by Kinoshita regarding the replacement of septins within a filament as well as the current literature and results of recent Y2H studies. The proposal is to perform the co-expression of complexes SEPT9-SEPT11-SEPT7-SEPT2, SEPT9-SEPT6-SEPT7; SEPT4-SEPT6-SEPT7 and SEPT4-SEPT8-SEPT7. It is anticipated that these combinations will allow us to investigate in detail the validity of Kinshita's rules. The determination of the crystal structures of these complexes will contribute significantly to our understanding of the structural details which control the formation of filaments by septins and how these proteins organize themselves into the correct structural arrangement, since so far only one structure of a heterocomplex at low resolution has been reported in the literature.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SILVA DO VALE CASTRO, DANIELLE KAROLINE; DE OLIVEIRA DA SILVA, SABRINA MATOS; PEREIRA, HUMBERTO D'MUNIZ; ALVES MACEDO, JOCI NEUBY; LEONARDO, DIEGO ANTONIO; VALADARES, NAPOLEAO FONSECA; KUMAGAI, PATRICIA SUEMY; BRANDAO-NETO, JOSE; ULIAN ARAUJO, ANA PAULA; GARRATT, RICHARD CHARLES. A complete compendium of crystal structures for the human SEPT3 subgroup reveals functional plasticity at a specific septin interface. IUCRJ, v. 7, n. 3, p. 462-479, . (10/20290-5, 16/19734-2, 16/04658-9, 12/00268-0, 14/15546-1)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SILVA, Sabrina Matos de Oliveira da. Investigation of Aspects Important in the Structural Assembly of Human Septin Filaments. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Química de São Carlos (IQSC/BT) São Carlos.

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